Project Summary Untargeted Resource The `exposome' represents every exposure, exogenous and endogenous, to which an individual is subjected from conception to death. While still beyond our grasp methodologically, the exposome concept recognizes that thousands of toxicants/ exposures impact development and health. It is not possible to develop validated biomarkers for all environmental exposures across a lifetime, especially given the rate at which new chemicals are being continuously formulated, but we can now begin to address our exposome. The Untargeted Analysis Resource aims to discover new chemicals and metabolites that are biomarkers of human health and disease risk. Furthermore, the downstream effects of environmental exposures also provide insight into the mechanisms of long-term harm and should be assessed. The Untargeted Analysis Resource of the Mount Sinai Hub will provide multiple state-of-the-art `omic' technologies for high-throughput and robust analyses that enable a systems-biology approach to investigating the presence and effects of environmental exposures through untargeted profiling of multiple measurable molecular targets. We will use well-established methods to generate large datasets and mine them for unique features of the `exposome', i.e., the range of interactions between environmental chemicals and human physiology, particularly during potential critical windows of vulnerability. The Untargeted Analysis Resource will integrate with the other Resources/Cores broadly through monthly Executive Steering Committee meetings of the full Hub team. Other interactions and collaborations include identifying new chemicals from the `top hits' derived from our untargeted screens. This is done by working closely with the Targeted Resource to undertake confirmatory analyses to identify the toxicants that constitute those hits. These in turn will be further analyzed by the Developmental Core as potential new biomarkers. We will also integrate with the Biological Response Indicators Resource as our proteomic and metabolomics screens will yield new biomarkers of effect. These too will be further assessed in collaboration with the Developmental Core potentially leading to new biomarkers. We will serve as expertise consultants with the Coordinating Center and PI/Clients on `omic' technologies. The Untargeted Resource will provide the computational support necessary to manage, format and structure our complex data sets for the data center. We will apply, develop and refine state-of-the-art QA/QC procedures with the other Lab Hubs, which will consider standard issues such as intra-class correlation. Finally, the Resource will also participate in the Annual Workshop Seminar program described in the Administrative Core.